Cell-to-cell contact can result in a variety of changes in the cell's physiology. For different cell types, this may include both the initiation as well as the cessation of cell growth and changes in the state of differentiation. This review examines in detail one such phenomenon, density-dependent inhibition of growth, which is observed with many fibroblasts in culture. Data are summarized which demonstrate that the cessation of growth at high cell density is in part a consequence of cell-to-cell contact. An approach to the study of the molecular basis of this phenomenon is presented based on the demonstration that plasma membranes, when bound to sparse growing cells, mimic contact inhibition of growth. The present status of attempts to purify plasma membrane proteins responsible for this effect are summarized, and the properties of these membrane proteins are compared to those of previously described "soluble" proteins that inhibit cellular growth.